Children and adolescents meeting DSM-III-R criteria for schizophrenia are being obtained through vigorous national recruiting. 26 subjects have participated to date int this study of the phenomenology, neurobiology and pharmacologic response to childhood onset schizophrenia. Over 650 medical records have been reviewed from which 123 patients appearing to meet DSM-III-R criteria for schizophrenia with onset of psychosis prior to age 12, were screened in person. A total of 31 received the diagnosis os schizophrenia at screening. A large number of children are receiving the diagnosis of schizophrenia inappropriately resulting in inappropriate treatment, even at major academic centers. Pilot family/genetic data indicate three cases (15%) are familial, not higher than seen with NIMH adult cases; a fourth subject had a 1:7 chromosomal translocation. Clinically, there is greater premorbid developmental delay particularly for language, than seen for the later onset disorder. Autonomic and eye tracking measures parallel these of adult, with a 9% small brain volume normalize on rescan after two years maintenance on clozapine, A double-blind comparison for this very ill treatment refractory population.